SCN5A Variant I925F

Summary of observed carriers, functional annotations, and structural context for SCN5A I925F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

10%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I925F is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-3.08 0.062 4.66 0.901 13 2

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 14 0 1 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near I925F.
Neighbour residue Distance (Å) Observed variants
891 11 I891N, I891T,
848 12 I848F,
856 13 V856L, V856L,
919 11
896 13 C896S, C896S,
895 9 L895F,
842 13
249 15 K249X,
894 11 I894M,
247 8 V247L, V247L,
240 12 V240M,
254 13
926 4
250 11
409 14 L409V, L409P,
928 7 L928P,
925 0 I925F,
227 12 L227P,
366 14
934 14
933 11
246 10
851 14 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
412 12 V412D,
897 13 G897R, G897R, G897E,
924 4 V924I,
927 8 N927S, N927K, N927K,
852 11
854 13 c.2559delT,
245 14 Q245K,
224 14 L224F,
845 11 c.2533delG,
244 11
892 14 F892I,
849 7
226 15 A226G, A226V,
921 6
922 6 V922I,
405 14
248 13
241 13
920 9
843 14 T843A,
930 7 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1459 15 c.4376_4379delTCTT
918 10
917 12 L917V, L917R,
239 13 I239V, I239V ,
230 14 I230V, I230T, I230M,
251 14
916 14
242 12 A242D,
929 6
408 12
253 15
847 12
846 9 L846R,
853 8
370 14 T370M,
923 8
899 13
850 10 V850M, c.2549_2550insTG,
411 14 V411M,
243 8
932 11
931 10